People who regularly culture animal cells become comfortable with standard techniques. However, the typical cycle of seeding cells at very low density in an excess of medium and harvesting just before the point of medium exhaustion is quite an un-physiologic process. Popular culture systems often take cells that originally grew attached to a porous matrix at high densities, with little variability in nutrient and oxygen supply, and adapt them to low-density, styrene-bound or amorphous suspension cultures. Although these methods are well understood and convenient, classical batch-style two-dimensional culture in T-flasks or three-dimensional suspension culture in shake-flasks and bioreactors really is not physiologically relevant.
A remarkable number of alternative culture approaches operating with such unusual mechanisms as rocking bags and depth filters have been introduced over recent years. These are often categorized by characteristics such as suspension/adherent or batch/continuous operation. However, most share two fundamental features: Cells are subjected to wide swings in nutrient, waste, and pH levels from seeding to harvest, and they are generally growing at highly cyclical but relatively low culture densities.
Until recently, the negative consequences of those highly artificial protocols were not well appreciated. But increasing demands of modern drug development, regenerative medicine, and fundamental scientific investigation have inspired the development of alternative approaches. Perfusion culture now exists in a number of (often quite distinct) implementations.
HFPB is a high-density, continuous perfusion culture system. Its hallmark component is a set of thousands of semipermeable hollow fibers in parallel array within a tubular housing or cartridge that is fitted with inlet and outlet ports. The fiber bundles are systematically potted (attached) at each end so that any liquid entering a cartridge will necessarily flow through their interior.
Early commercially available systems from companies as Amicon (now part of Millipore Corporation, www.millipore.com/amicon), Endotronics (now Biovest international, www.biovest.com), and TERUMOBCT www.terumobct.com and offered poor gross filtration rates. Moreover, early units had insufficient nutrient and waste exchange to support the extended culture. Further, large-scale cell culture depends on the mass transfer rates of poorly soluble oxygen, which was the Achilles' heel of early attempts at larger-scale hollow-fiber systems.